The American Cancer Society predicts over 100,000 women in the United States will be diagnosed with breast cancer in 2008. Between 60-70% of those diagnosed will use complementary or alternative medicine (CAM). We have evidence that tumor bearing mice given oral sodium bicarbonate (NaHCOS) demonstrate a significant reduction in metastatic lesions (p<0.001) and improved survival (p<0.02), compared to untreated tumor bearing mice. These findings implicate sodium bicarbonate as potential CAM in treatment of breast cancer. This Mentored Research Scientist Development Award (K01) application proposes to extend the candidate's training in cancer research with emphasis on bioimaging, pathophysiology (tumor microenvironment), pharmacology, biostatistics and integrative medicine. The concepts and skills obtained from this training will be applied to investigating the role of tumor pH on metastatic potential in breast cancer. The current project focuses on the recent observation that spread of metastatic disease can be reduced through inhibition of tumor acidosis through increased buffering. This is consistent with the "acid-mediated invasion" hypothesis, which states that growth of metastases is stimulated by locally acidic pH which upregulates expression or activity of specific effectors (proteases/angiogenic factors) known to modulate tumor progression. The proposed work will investigate the effects of pH on tumor behavior and the mechanisms involved in breast cancer along the following Aims: 1) investigate the physiological effects of selective alkalinization on the inhibition of tumor metastases;2) investigate the direct effects of acidity on invasion and metastases;and 3) examine the effect of selective alkalinization on the expression/activity of specific metastatic effectors, and the ability of inhibitors in combination with oral bicarbonate to reduce expression/activity of these factors. The applicant will train under the mentorship of Arizona Cancer Center scientists with specific overlapping expertise relevant to the proposed experiments, and who have nationally funded programs in cancer research. The training will be used to develop a research program at the Arizona Cancer Center focused on discovery and development of therapeutic strategies in cancer treatment.